Unlicensed and Off-Label Drug Use in Children Before and After Pediatric Governmental Initiatives

Abstract

OBJECTIVES: Governmental agencies (US Food and Drug Administration and European Medicines Agency) implemented initiatives to improve pediatric clinical research, starting in 1997 and 2007, respectively. The aim of this review was to quantify the unlicensed and off-label drug uses in children before and after these implementations. METHODS: Literature review of unlicensed and off-label drug uses was performed on PubMed and Google-Scholar from 1985 to 2014. Relevant titles/abstracts were reviewed, and articles were included if evaluating unlicensed/off-label drug uses, with a clear description of health care setting and studied population. Included articles were divided into 3 groups: studies conducted in United States (before/after 2007), in Europe (before/after 2007), and in other countries. RESULTS: Of the 48 articles reviewed, 27 were included. Before implementation of pediatric initiatives, global unlicensed drug use rate in Europe was found to be 0.2% to 36% for inpatients and 0.3% to 16.6% for outpatients. After implementation, it marginally decreased to 11.4% and 1.26% to 6.7%, respectively. Concerning off-label drug use rates, it was found to be 18% to 66% for inpatients and 10.5% to 37.5% for outpatients before the implementation. After implementation, it decreased marginally to 33.2% to 46.5% and to 3.3% to 13.5%, respectively. In other countries, unlicensed and off-label drug use rates were found to be, respectively, 8% to 27.3% and 11% to 47%. CONCLUSIONS: Governmental initiatives to improve clinical research conducted in children seem to have had a marginal effect to decrease the unlicensed and off-label drug uses prevalence in Europe.